PANITUMUMAB for Metastatic colorectal cancer

Inclusion criteria

• {"criterion_text":"- 1) Man or woman of at least 18 years old."}
• {"criterion_text":"- 2) Capable to understand, sign and date an informed consent approved by an IEC."}
• {"criterion_text":"- 3) Histologically confirmed adenocarcinoma of the left colon or rectum (originated in the splenic flexure, descending colon, sigmoid colon, or rectum) in patients with unresectable or non-potentially resectable (not amenable to radical surgery of metastases at the study inclusion) metastatic (M1) disease."}
• {"criterion_text":"- 4) Patients who had wild-type RAS status confirmed as per standard of care according to international guidelines prior to first-line initiation. *RAS analysis should include at least KRAS exons 2, 3 and 4 (codons 12, 13, 59, 61, 117 and 146) and NRAS exons 2, 3 and 4 (codons 12, 13, 59, 61 and 117)"}
• {"criterion_text":"- 5) At least one measurable lesion per RECIST criteria (version 1.1)."}
• {"criterion_text":"- 6) ECOG performance status < 2."}
• {"criterion_text":"- 7) Adequate bone marrow function: neutrophils ≥1.5 x109/ L; platelets ≥100 x109/L; haemoglobin ≥9 g/dL."}
• {"criterion_text":"- 8) Hepatic, renal and metabolic function as follows: - Total bilirubin count ≤1.5 x upper limit of normal (ULN), serum glutamic pyruvic transaminase/alanine aminotransferase (SGPT/ALT) and serum glutamic oxaloacetic transaminase/aspartate aminotransferase (SGOT/AST) ≤2.5 x ULN (5 x ULN for subjects with liver involvement of their cancer) - Renal function, calculated as creatinine clearance or 24-hour creatinine clearance ≥50 mL/min."}

Exclusion criteria

• {"criterion_text":"- 1) History of prior or concurrent central nervous system metastases."}
• {"criterion_text":"- 10) History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on baseline chest computed tomography (CT)."}
• {"criterion_text":"- 11) Treatment for systemic infection < 14 days before the start of study treatment."}
• {"criterion_text":"- 12) Active acute or subacute intestinal occlusion and/or active inflammatory bowel disease or another bowel disease that causes chronic diarrhoea (defined as grade ≥2 diarrhoea according to NCI-CTCAE version 4.03)."}
• {"criterion_text":"- 13) Clinically significant peripheral sensory neuropathy."}
• {"criterion_text":"- 14) Evidence of previous acute hypersensitivity reaction, of any grade, to any component of the treatment."}
• {"criterion_text":"- 15) Known mutation in the UGT1A1 gene or known dihydropyrimidine deficiency syndrome."}
• {"criterion_text":"- 16) Recent (< 6 months before the start of study treatment) gastroduodenal ulcer active or uncontrolled."}
• {"criterion_text":"- 17) Recent (< 6 months before the start of study treatment) pulmonary embolism, deep vein thrombosis, or another significant venous event."}
• {"criterion_text":"- 18)\tPre-existing bleeding diathesis and/or coagulopathy with exception of well-controlled anticoagulation therapy (< 6 months before the start of study treatment)."}
• {"criterion_text":"- 19) Recent (< 28 days prior to inclusion in the study) major surgical procedure (excluding diagnostic biopsy, placement of a central venous catheter, colonic stents, or any minor surgery), open biopsy, or significant traumatic injury not yet recovered from prior major surgery."}
• {"criterion_text":"- 2) History of another primary cancer, except: curatively treated in situ cervical cancer, or curatively resected non-melanoma skin cancer, or other primary solid tumour curatively treated with no known active disease present and no treatment administered for ≥ 5 years before randomization."}
• {"criterion_text":"- 20)\tHistory of any disease that may increase the risks associated with study participation or may interfere with the interpretation of study results."}
• {"criterion_text":"- 21)\tKnown positive test for human immunodeficiency virus infection, hepatitis C virus, and chronic active hepatitis B infection."}
• {"criterion_text":"- 22)\tAny disorder that compromises the patient’s ability to provide written informed consent and/or comply with study procedures."}
• {"criterion_text":"- 23) Any investigational agent <30 days prior to inclusion."}
• {"criterion_text":"- 24) Pregnant or breastfeeding women."}
• {"criterion_text":"- 25)\tFull dose radiotherapy <28 days prior to inclusion in the study. Short course radiotherapy for local control of primary tumor or other palliative indication is allowed."}
• {"criterion_text":"- 26)\tMale or female of childbearing age who do not agree with taking adequate contraceptive precautions, (i.e. use double barrier contraception (such as diaphragm plus condoms) or abstinence during the course of the study and for 6 months after the last administration of study drug for women and men."}
• {"criterion_text":"- 27) The patient is unwilling or unable to meet the requirements of the study."}
• {"criterion_text":"- 28)\tPsychological, geographical, familiar or sociological conditions that potentially prevent compliance with the study protocol and follow-up schedule."}
• {"criterion_text":"- 3) Prior chemotherapy or other systemic anticancer therapy for treatment of metastatic colorectal carcinoma (including adjuvant QT for resected stage IV disease)"}
• {"criterion_text":"- 4)\tPrior adjuvant chemotherapy for colorectal cancer (stage I, II or III) terminated less than 6 months before metastatic disease was diagnosed."}
• {"criterion_text":"- 5) Unresolved toxicities of a previous systemic treatment that, in the opinion of the Investigator, make the patient unfit for inclusion."}
• {"criterion_text":"- 6)\tPrior use (as monotherapy or adjuvant treatment) of anti-EGFR antibody therapy (e.g.cetuximab), anti-VEGF or small molecule tyrosine kinase inhibitors (e.g. regorafenib)."}
• {"criterion_text":"- 7)\tPrior approved or experimental antitumoral treatment ≤ 30 days before inclusion.Hormonal sustitutive treatment is allowed."}
• {"criterion_text":"- 8) Significant cardiovascular disease including unstable angina or myocardial infarction within 12 months before initiating study treatment or history of ventricular arrhythmia."}
• {"criterion_text":"- 9) Uncontrolled hypertension."}

Primary endpoints

• {"endpoint_text":"- 36-month PFSR defined as the number of patients, who at 36 months after randomization, have not had second† or first†† disease progression nor died (due to any cause), over the total number of evaluable patients. **To see the full text please refer to the protocol section 4.1.","definition_or_measurement_approach":"Defined as the number of patients who, 36 months after randomization, have not had second or first disease progression nor died (due to any cause) over the total number of evaluable patients; see protocol section 4.1 for full details."}

Secondary endpoints

• {"endpoint_text":"- 36-month OSR defined as the number of patients who at 36 months after randomization have not died over the total number of evaluable patients.","definition_or_measurement_approach":"Defined as the number of patients who, 36 months after randomization, have not died over the total number of evaluable patients."}
• {"endpoint_text":"- OS defined as the time from randomization to the date of death (due to any cause), with patients alive or lost to follow-up at the analysis data cut-off date censored at their last contact date.","definition_or_measurement_approach":"Time from randomization to date of death (any cause); censoring at last contact for alive/lost-to-follow-up at data cut-off."}
• {"endpoint_text":"- Total PFS defined as the time from randomization to second disease progression (i.e. progression during the second-line treatment)* or death (due to any cause). Patients who start a new antitumoral treatment different to specified in the protocol will be considered censored at date of last tumor assessment. Patients with surgery of tumor will be follow to PFS until documented progression disease or death for any cause. **To see the full text please refer to the protocol section 4.1.","definition_or_measurement_approach":"Time from randomization to second disease progression (during second-line) or death; patients starting an unplanned new antitumoral treatment are censored at last tumor assessment; surgical patients followed until documented progression or death."}
• {"endpoint_text":"- PFS in first-line treatment defined as the time from randomization to disease progression or death (due to any cause) during first-line treatment. Patients who start a new antitumoral treatment different to specified in the protocol will be considered censored at date of last tumor assessment. **To see the full text please refer to the protocol section 4.1.","definition_or_measurement_approach":"Time from randomization to progression or death during first-line treatment; censoring at last tumor assessment if new unplanned treatment initiated."}
• {"endpoint_text":"- PFS in second-line treatment defined as the time from the date of second-line treatment initiation to disease progression or death (due to any cause) during second-line treatment. Patients who start a new antitumoral treatment different to what is specified in the protocol will be considered censored at the date of last tumor assessment. **To see the full text please refer to the protocol section 4.1.","definition_or_measurement_approach":"Time from second-line treatment start to progression or death during second-line treatment; censoring at last tumor assessment if new treatment initiated."}
• {"endpoint_text":"- Time to first-line treatment failure defined as the time form randomization to disease progression, death (due to any cause) or discontinuation due to toxicity during first-line treatment.","definition_or_measurement_approach":"Time from randomization to progression, death, or discontinuation due to toxicity during first-line treatment."}
• {"endpoint_text":"- Time to second-line treatment failure defined as the time from the date of second-line treatment initiation to disease progression, death (due to any cause) or discontinuation due to toxicity during second-line treatment.","definition_or_measurement_approach":"Time from start of second-line treatment to progression, death, or discontinuation due to toxicity during second-line treatment."}
• {"endpoint_text":"- Proportion of patients with an objective response (complete or partial response) per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 criteria in first-line treatment and in second-line treatment.","definition_or_measurement_approach":"Proportion of patients achieving complete or partial response per RECIST 1.1 during first-line and second-line treatments."}
• {"endpoint_text":"- Proportion of patients with ETS in first-line treatment and in second-line treatment. ETS will be defined as a reduction in tumour size ≥30% (RECIST 1.1 criteria) at the first evaluation (i.e. week 12)","definition_or_measurement_approach":"ETS defined as ≥30% reduction in tumour size per RECIST 1.1 at first evaluation (week 12); proportion of patients meeting this criterion in first- and second-line."}
• {"endpoint_text":"- DpR measured as the maximum decrease in target measurement (RECIST 1.1 criteria) during the complete course of evaluation in first-line treatment and in second-line treatment.","definition_or_measurement_approach":"Maximum decrease in target lesion measurements per RECIST 1.1 during evaluation period in first- and second-line treatments."}
• {"endpoint_text":"- Proportion of patients with disease control (complete, partial response or stable disease) in first-line treatment and in second-line treatment.","definition_or_measurement_approach":"Proportion of patients achieving complete response, partial response, or stable disease per RECIST 1.1 in first- and second-line."}
• {"endpoint_text":"- Duration of disease control defined as time from first confirmed disease control to disease progression per RECIST 1.1 criteria or death (due to any cause) in first-line treatment and in second-line treatment. For patients with disease control who have not progressed or died at last observation, duration of disease control will be censored at their last evaluable disease assessment date.","definition_or_measurement_approach":"Time from first confirmed disease control to progression (RECIST 1.1) or death; censoring at last evaluable disease assessment if no event."}
• {"endpoint_text":"- Duration of response defined as time from first confirmed objective response to disease progression per RECIST 1.1 criteria or death in first-line treatment and in second-line treatment. For patients with response who have not progressed or died at last observation, duration of response will be censored at their last evaluable disease assessment date.","definition_or_measurement_approach":"Time from first confirmed objective response to progression (RECIST 1.1) or death; censoring at last evaluable assessment if no event."}
• {"endpoint_text":"- Time to response in first-line treatment defined as the time from randomization to the date of first confirmed objective response per RECIST 1.1 criteria during first-line treatment.","definition_or_measurement_approach":"Time from randomization to first confirmed objective response per RECIST 1.1 during first-line treatment."}
• {"endpoint_text":"- Time to response in second-line treatment defined as the time from the date of second-line treatment initiation to the date of first confirmed objective response per RECIST 1.1 criteria during second-line treatment.","definition_or_measurement_approach":"Time from second-line treatment initiation to first confirmed objective response per RECIST 1.1 during second-line treatment."}
• {"endpoint_text":"- Safety assessment will consist of monitoring adverse events (AEs), including AEs of special interest, serious AEs (SAEs) and laboratory safety parameters. AEs will be graded according to National Cancer Institute - Common Terminology Criteria for Adverse Events (NCICTCAE) version 4.03.","definition_or_measurement_approach":"Monitoring of AEs, SAEs and laboratory safety parameters; AEs graded per NCI-CTCAE v4.03."}

Portugal

Earliest CTIS Part Ii Submission Date

20-03-2024

Latest Decision Or Authorization Date

27-11-2025

Processing Time Days

617

Number Of Sites

6

Number Of Participants

70

Spain

Earliest CTIS Part Ii Submission Date

20-03-2024

Latest Decision Or Authorization Date

12-02-2026

Processing Time Days

694

Number Of Sites

50

Number Of Participants

346

Primary sponsor

Full Name

Asociacion Grupo Tratamiento De Tumores Digestivos

Organisation Type

Patient organisation/association

Country Of Registered Address

Spain

Third parties

• {"country":"Spain","full_name":"Hospital Del Mar","duties_or_roles":"Laboratory: Receipt, Storage and DNA extraction-NGS analysis; code:4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Spain","full_name":"Pivotal S.L.","duties_or_roles":"codes:1,10,11,12,6,7,8","organisation_type":"Pharmaceutical company"}